Introduction: Deep bowel endometriosis is a rare, clinically challenging diagnosis mimicking many gastrointestinal diseases. There are no clear guidelines for the evaluation of patients with suspected bowel endometriosis, therefore a high index of suspicion is warranted. Case Description/Methods: A 39 year old female with a history remarkable for fibroidectomy and constipation presents for rectal bleeding and discomfort for 1 month. In 2012, FOBT was positive and colonoscopy findings were significant for a solitary rectal ulcer. Biopsies showed inflammation. Due to persistent symptoms, a flexible sigmoidoscopy (2013) with repeat biopsies confirmed the diagnosis of deep bowel endometriosis located at the anterior portion of the rectum. Hormonal therapy offered complete resolution of her symptoms. In 2021, due to menopausal symptoms, hormonal therapy was discontinued leading to recurrence of symptoms and new onset right sided lumbosacral shingles. Colonoscopy findings were significant for luminal narrowing and nodularity at the anterior portion of the rectum. Biopsies were nonspecific. Discussion: Given that endometriosis rarely infiltrates the submucosa or mucosa (6.4% of cases), initial colonoscopy and biopsy findings may be nonspecific. Hence, an initial inappropriate diagnosis may occur, demonstrating how challenging this diagnosis may become. Even though the gold standard for diagnosis is direct laparoscopic visualization or tissue diagnosis, imaging modalities such as transvaginal and transrectal US and MRI may diagnose and determine the extent of deep bowel endometriosis. Response to hormonal treatment in deeply infiltrating bowel endometriosis is unpredictable and may require a surgical approach. The natural course of bowel endometriosis has not been formally established. Some authors describe inactive endometriosis as a nodular and fibrotic lesion associated with adhesions and strictures. This correlated with the findings of our patient's latest colonoscopy. Association of endometriosis with rheumatological and autoimmune disorders have been established, where theories based on genetic dysregulation of immune, adhesion, and inflammatory processes take part in the disease pathology. This may explain the greater likelihood of shingles reactivation, such experienced by our patient, during an immunocompromised state such as menopause. Even though deep bowel endometriosis is poorly understood, a high index of suspicion is crucial to offer patients a correct diagnosis and appropriate treatment options.Figure 1.: Deep bowel endometriosis. (Top, left to right) Colonoscopy findings from 2012 (first 2 images) and 2013 respectively showing an abnormal mucosal lesion in the proximal portion of the anterior rectum. (Bottom, left to right) Colonoscopy findings from 2021 showing mucosal nodularity in the proximal portion of the anterior rectum.